运动调控FGF21在改善肥胖相关代谢性疾病中的作用  

The Role of Exercise-regulated FGF21 in Improving Obesity-related Metabolic Diseases

作　　者：杨嘉培 杨桂荣 秦莲 王心壮 朱光明 李良鸣[1] 杨文琦 YANG Jia-Pei;YANG Gui-Rong;QIN Lian;WANG Xin-Zhuang;ZHU Guang-Ming;LI Liang-Ming;YANG Wen-Qi(Guangzhou Sport University,Guangzhou 510500,China)

机构地区：[1]广州体育学院,广州510500

出　　处：《生物化学与生物物理进展》2023年第11期2591-2603,共13页Progress In Biochemistry and Biophysics

基　　金：广东省教育厅,广东省普通高校重点领域专项(生物医药与健康)(2021ZDZX2054)资助项目。

摘　　要：肥胖是糖尿病、脂肪肝、心血管疾病等慢性代谢性疾病发生发展的重要风险因素。运动可以改善肥胖,对相关代谢性疾病的预防与康复具有积极作用。成纤维细胞生长因子21 (fibroblast growth factor 21,FGF21)是一种对机体能量稳态、糖脂代谢有积极调控作用的内分泌因子,是代谢性疾病预防和治疗的有效靶点之一。FGF21抵抗是机体对FGF21反应性减弱的现象,表现为靶组织生物学效应降低,机体FGF21代偿性合成增加。这可能是由FGF21受体(fibroblast growth factor receptors,FGFRs)和β-klotho蛋白(β-klotho,KLB)表达减少或敏感性降低所致。肥胖患者常出现FGF21抵抗,改善FGF21抵抗是治疗肥胖及相关代谢性疾病的新思路。运动不仅可以增加部分组织FGF21表达量,还可以刺激FGFRs与KLB的表达来敏化FGF21的作用,改善FGF21抵抗。Obesity is an important risk factor for the development and progression of chronic metabolic diseases such as diabetes,fatty liver and cardiovascular diseases.Endocrine factor fibroblast growth factor 21(FGF21),which has multiple beneficial effects on energy homeostasis and glucose and lipid metabolism,serves as a promising therapeutic target for obesity and related metabolic diseases.FGF21 relies on high-affinity interaction with β-klotho(KLB) for recruitment and localization to the cell surface,where it engages FGF receptors(FGFRs).Obesity has been demonstrated as a FGF21 resistant state,in which circulating FGF21 levels are elevated while its downstream signaling and action are impaired.This may be caused by the decreased expression of KLB and FGFRs.Improving FGF21 resistance emerges as a new therapeutic strategy for obesity and its associated diseases.Exercise has long been considered as a cornerstone for the prevention and treatment of obesity and its related metabolic diseases.Evidence is mounting that FGF21 plays an important role in exercise-mediated health promotion.Exercise not only increases the expression of FGF21 in adipose tissue,skeletal muscle and heart,but also stimulates the expression of FGFRs and KLB to sensitize the effect of FGF21 and improve FGF21 resistance in target tissues such as adipose tissue.Knockout experiments confirmed FGF21 as a key mediator of exercise-induced improvements in obesity and related metabolic diseases.There are many issues that need further study.Circulating FGF21 is mainly derived from the liver.However,uncertainty about the long-term effects of exercise on liver FGF21 expression still remains.In most research,a single pharmacological dose of FGF21 was used to determine FGF21 sensitivity.Whether exercise improves the physiological effects and the long-term effects of FGF21 also needs further investigation.Clariying these issues has important implications for our understanding of how exercise ameliorates obesity and its related metabolic diseases through FGF21 sign

关 键 词：运动 FGF21 肥胖 代谢性疾病 

分 类 号：G804[文化科学—运动人体科学] R87[文化科学—体育学]